Aspiration Thrombectomy System and Methods for Thrombus Removal with Aspiration Catheter

ABSTRACT

An aspiration thrombectomy system including an aspiration catheter having a proximal portion, a distal end and a lumen extending through the catheter, a vacuum source fluidically coupled to the catheter, a vacuum valve connected between the vacuum source and the proximal portion of the catheter to control a vacuum flow in the catheter lumen, a vent valve fluidically coupled to the proximal portion of the catheter, the vent valve being configured to control a flow of a vent fluid in the catheter lumen, and a controller configured to open and close the vacuum valve and the vent valve in a predetermined cycle to change a level of vacuum at the distal end of the catheter and to control fluid flow in and out from the distal end of the catheter.

PRIORITY

This application is a continuation under 35 U.S.C. § 120 of U.S. patentapplication Ser. No. 17/687,435, filed 4 Mar. 2022, which is acontinuation under 35 U.S.C. § 120 of U.S. patent application Ser. No.17/387,704, filed 28 Jul. 2021, which is a continuation under 35 U.S.C.§ 120 of U.S. patent application Ser. No. 16/988,556, filed 7 Aug. 2020,which claims the benefit under 35 U.S.C. § 365(c) of PCT InternationalApplication No. PCT/US2019/043095, filed 23 Jul. 2019, which claims thebenefit under 35 U.S.C. § 119(e) of U.S. Provisional Patent ApplicationNo. 62/778,708, filed 12 Dec. 2018, and of U.S. Provisional PatentApplication No. 62/702,804, filed 24 Jul. 2018, which are incorporatedherein by reference.

TECHNICAL FIELD

The present invention relates generally to the field of medical devicesand methods. More specifically, the invention described herein relatesto devices and methods for controlling clot removal from a patient'svasculature by aspiration thrombectomy.

BACKGROUND

Stroke is a significant cause of disability and death, and a growingproblem for global healthcare. More than 700,000 people in the UnitedStates alone suffer a stroke each year, and of these, more than 150,000people die. Of those who survive a stroke, roughly 90% will suffer longterm impairment of movement, sensation, memory, or reasoning, rangingfrom mild to severe. The total cost to the U.S. healthcare system isestimated to be over $50 billion per year.

Stroke may be caused by a blockage in a cerebral artery resulting from athromboembolism (referred to as an “ischemic stroke”), or by a ruptureof a cerebral artery (referred to as a “hemorrhagic stroke”).Hemorrhagic stroke results in bleeding within the skull, limiting bloodsupply to brain cells, and placing harmful pressure on delicate braintissue. Blood loss, swelling, herniation of brain tissue, and pooling ofblood that results in formation of clot mass inside the skull allrapidly destroy brain tissue. Hemorrhagic stroke is a life-threateningmedical emergency with limited treatment options.

Aside from cerebral stroke, thromboembolism throughout the vasculature,in both arterial and venous circulation, is characteristic of numerouscommon, life-threatening conditions. Examples of potentially fataldiseases resulting from thrombotic occlusion include pulmonary embolism,deep vein thrombosis, and acute limb ischemia. Acute pulmonary embolismis a significant cause of death in the United States, with roughly300,000 patients dying each year. Pulmonary embolism can be acomplication from deep vein thrombosis, which has an annual incidence of1% in patients 60 years and older. All of the aforementioned diseasesare examples of conditions in which treatment may include aspiration orevacuation of clot and/or blood.

Of particular interest to the present invention, the Penumbra System®mechanical thrombectomy system is a fully integrated system designedspecifically for mechanical thrombectomy by aspiration. It is intendedfor revascularization of patients with acute ischemic stroke secondaryto intracranial large vessel occlusion. A comparable system designed forthe peripheral and coronary vasculature, the Indigo® System is also amechanical thrombectomy aspiration system, designed forrevascularization of patients with thrombotic occlusion of theperipheral vasculature. Both the Penumbra System and the Indigo Systemare commercially available at the time of filing the present provisionalpatent application and include aspiration or reperfusion catheters,aspiration tubing, other accessories, and an aspiration pump (sold underthe tradename: Pump MAX′ aspiration pump or Penumbra Engine™ aspirationpump) for connection to the aspiration tubing and aspiration catheters.As illustrated in FIG. 1 , the Pump MAX′ aspiration pump 10 includes abase unit 12 which encloses a vacuum pump (not shown) which operates offof line voltage. The base unit has an on-off switch 14 and a separateknob 16 for adjusting the level of vacuum provided by the pump. Thevacuum level can be read on a pressure gauge 18. Blood and clot aredrawn into a collection canister 20 from an aspiration tube 22 (shown inbroken line) which is connected to a reperfusion catheter (notillustrated) which has been introduced to the vasculature of a patientto aspirate clot. The blood and clot are drawn into the collectioncanister by a partial vacuum which is provided by a vacuum connector 28on the base unit 12 which is connected to the vacuum pump, not shown.The vacuum from vacuum connector 28 is applied to a vacuum port 24 on aremovable lid 26. The vacuum connector 28 is connected to the vacuumport 24 by an external vacuum tube 30.

Although very effective, clot aspiration using the Indigo Systemmechanical thrombectomy apparatus or other similar vacuum-assistedthrombectomy systems must sometimes be terminated due to the risk ofexcessive blood loss by the patient, especially when using largeaspiration catheters. During aspiration thrombectomy, when the cathetertip falls out of contact with the thrombus or other occlusive material,the tip is exposed to healthy blood and full flow ensues. Under suchconditions, the blood loss rate is excessive, and in some cases, mayresult in premature termination of the procedure. In one example, duringa procedure when the catheter enters healthy blood and full flow ensues,the blood loss rate is in the range of 20-25 cc per second with an 8French size catheter. With a maximum tolerable blood loss of 300-1000mL, the catheter cannot run in unrestricted mode for more thanapproximately 20 to 50 seconds. When a physician operates the systemmanually, the aggregate blood loss may reach an unacceptable levelbefore sufficient clot is removed. In addition, reliably identifyingwhether the tip of the catheter is in contact with clot or isundesirably aspirating healthy, clot-free blood is a significantproblem, and such manual control is not optimum.

During other procedures using the Penumbra System, such as, for example,neurovascular procedures for treatment of ischemic stroke, excessiveremoval of blood is less of a risk, and the primary focus of theprocedure is maximization of removal of occlusive material. Optimizingboth technique and aspiration control are of upmost importance forsuccessful removal of occlusive material.

Therefore, it would be desirable to provide improved methods andapparatus for controlling the aspiration of thrombus and clot usingaspiration catheters in combination with pumping consoles. It would beparticularly useful to provide systems and methods which limit bloodloss during such aspiration procedures such as by automatically stoppingaspiration while the aspiration catheter is not in contact with clot orthrombus. Additionally, it would be desirable to provide systems andmethods which optimize system performance, and procedures for removal ofocclusive material. At least some of these objectives will be met by theinventions described herein below.

The Penumbra System® as it is commercially available at the time offiling this provisional patent application is described in a brochureentitled “Science of Aspiration: The Penumbra System® Approach.”Relevant patents and patent publications include: U.S. Pat. No.4,574,812; U.S. Pat. Nos. 5,624,394; 6,019,728; 6,283,719; 6,358,225;6,599,277; 6,689,089; 6,719,717; 6,830,577; 8,246,580; 8,398,582;8,465,467; 8,668,665; 9,248,221; US2003/0050619; US2010/094201;US2014/323906; US2014/276920; US2016/0220741; US2017/0238950;US2017/049470; WO2014/151209; and WO2010/045178.

SUMMARY OF PARTICULAR EMBODIMENTS

The present invention provides systems and methods that improve catheteraspiration by enabling a longer procedure, by enhancing the ingestion ofocclusive material, or both. In some examples, the amount of fluidflowing through an aspiration catheter under vacuum aspiration ismonitored to determine whether the flow is unrestricted, restricted, orclogged. Depending on the determined flow state, the present inventionmay employ different techniques and methods to improve catheteraspiration. In one example, unrestricted flow is detected, andaspiration is automatically and temporarily restricted for blood savingpurposes. This may beneficially prolong the time available to performthe procedure and thereby allow more complete removal of occlusivematerial. In another example, restricted flow is detected, and fullvacuum aspiration is automatically applied. In yet another example, aclogged catheter is detected, and pulsed aspiration is automaticallyapplied. This may beneficially enhance the ingestion of large, tough, orotherwise troublesome occlusions. Alternatively, pulsed aspiration, fullaspiration, or restricted aspiration may be applied on demand by a userof the present invention.

In one example, the systems and methods of the present invention addressthe problem of excessive blood loss through dynamic aspiration cycling.The nature and flowability of the material being withdrawn by theaspiration catheter is monitored so that the system can either allowcontinuous aspiration when in clot, or sampling of extraction rate todetermine whether the tip of the catheter is in contact with clot, inorder to reduce the risk of excess blood loss. While determining andmonitoring of blood flow rate is disclosed in the exemplary embodimentsbelow, other measurements of the flowability and/or structuralcomposition of the aspiration effluent, such as monitoring thecollection chamber's volume, monitoring the collection chamber's fillrate, visually monitoring the aspiration tubing (clot is darker thanfresh blood), or placing a strain gauge on aspiration tubing, could alsobe used.

The systems and methods of the present invention may respond tovariations in flow rate, pressure, differential pressure, or otherindicators of the composition of the material inside or adjacent to anaspiration catheter in a sub-second time frame to limit the unnecessaryaspiration of blood during a thrombectomy procedure. The presentinvention may be useful with any thrombectomy, embolectomy, atherectomy,or other catheter or probe system where blood and clot are withdrawnwholly or partially by application of a vacuum to the proximal end ofany reperfusion, aspiration catheter or probe for the purpose of clotextraction.

In a first aspect, the present invention provides a vacuum aspirationcontrol system for use with a vacuum source and an aspiration catheter.The system comprises a flexible connecting tube, an on-off valve, asensing unit, and a controller. The connecting tube is linear in anunconstrained configuration and is configured to connect the vacuumsource to an aspiration lumen in the aspiration catheter. The on-offvalve is configured to be operatively connected to the connecting tube,and the sensing unit is configured to determine flow rate within theconnecting tube and to produce a signal representative of such flow,typically as either unrestricted flow, restricted flow, or clogged. Thecontroller is connected to receive the signal representative of flowthrough the connecting tube and to open and close one or more on-offvalve(s) in response to the signal. In one example, the controller isconfigured to automatically close the on-off valve to stop flow throughthe connecting tube when the signal indicates unrestricted flow, e.g.that primarily healthy blood or blood free of vessel-obstructing clot isflowing through the connecting tube and/or that the catheter issubstantially free from contact with clot or other occlusive material.In another example, the controller is configured to initiate pulsedaspiration when the signal indicates a clog, which may be caused by someocclusive material in or adjacent to the catheter or connecting tubing.

The controller is typically further configured to automatically open theon-off valve at a predetermined interval to sample effluent materialthrough the connecting tube and the valve will typically only remainopen if the signal indicates a return to clot. The controller algorithmis capable of deciphering the difference between healthy blood and clotindependent of aspiration source and the inner diameter of the attachedcatheter.

The sensing unit may comprise any one or more of a variety of sensors,including differential pressure sensors, acoustic (including ultrasonic)flow sensors, optical flow sensors, thermal flow sensors, magnetic flowsensors, sensors which detect circumferential expansion of theconnecting tube, and the like. While differential pressures aredescribed in more detail below, it will be appreciated that any sensingunit capable of detecting when flow or extraction rate through theconnecting tube is excessive and/or clogged, would be suitable for usein the present invention.

In exemplary embodiments, the sensing unit comprises a pair of pressuresensors at spaced-apart locations along the connecting tube to measuredifferential pressure. The controller can calculate flow based on thedifferential pressure and, from this, determine whether the calculatedflow rate indicates unrestricted flow, restricted flow, or a clog.

In another embodiment, the sensing unit uses optical sensors thatmeasure transmission, absorption, or both of light to characterize thecontents flowing through the connecting tube. In one such example,visible light is used determine whether flow contains clot or isprimarily clot-free. Typically, flow with clot is darker, which isdetectable by optical sensors. Alternatively, the optical sensors mayinfrared, ultraviolet, visible light, or some such combination toanalyze contents within the connecting tubing.

In another embodiment, the sensing unit uses circumferential expansionsensors to determine the contents flowing through the connecting tube.The internal pressure of the connecting tubing and the contents flowingthrough it effect the circumference of the connecting tubing. Understrong vacuum, such as during a clog, the tubing may maximally contract.During high flow of primarily clot-free blood, the tubing may contractonly slightly. During restricted flow, the clots and blood may cause arelative expansion of the connecting tubing.

The on-off valve may also take a variety of specific forms. Typically,regardless of form, the on-off valve will comprise an actuator, such asa solenoid actuator, that is powered to open the valve. The valve itselfmay take a variety of forms, including a pinch valve, an angle valve, orany one of a variety of other valves that provide actuation.Alternatively, the manual on-off valve may be provided that allows auser to initiate and/or terminate functions and features of the presentinvention.

In further exemplary embodiments, the controller may be configured toopen the valve and hold the valve open until a flow pattern whichindicates unrestricted flow is detected whereupon the controller closesthe valve. The controller may be further configured to automaticallyre-open the on-off valve. For example, in what may be referred to as“sampling mode”, the controller may be further configured toperiodically sample, or test flow to re-characterize flow and determineif it is safe to recommence aspiration. For example, the controller mayperiodically test flow by opening the on-off valve for a fixed timeinterval, in one embodiment 150 milliseconds, to establish a “test”flow. The test flow is characterized and, if it so indicates, the on-offvalve may be reopened into a “treatment” mode to allow continuedaspiration treatment. If the system characterizes the flow asunrestricted, e.g. excessive, then the system will dwell in a closedconfiguration for a fixed time interval, in one embodiment between aquarter second and two seconds, before an additional pressuredifferential sample is taken.

In other instances, however, the controller may not be configured toautomatically reestablish flow when safe conditions have been reached.For example, the controller may be configured to allow a user toreposition the aspiration catheter and, after repositioning, manuallyopen the on-off valve (typically by actuating a switch which causes thecontroller to open the on-off valve) to resume aspiration treatment. Insuch instances, the controller may immediately return to the “samplingmode,” however, and if the reestablished flow is characterized asunrestricted flow, the controller will again close the on-off valve, andthe user can again reposition the aspiration catheter in order to engageclot and manually resume aspiration. Such systems will typically providea manual switch which allows the user to manually open the on-off valve.

The controller may be configured to control two or more valves. In oneexample, the controller controls a first on-off valve between anaspiration catheter and a vacuum source and a second on-off valvebetween an aspiration catheter and a pressure source with a pressure atleast above that of the vacuum source. The controller may alternatebetween opening the first on-off valve and the second on-off valve togenerate pressure variations within an aspiration catheter or tubingadjacent to such a catheter. The controller may sample flow while thefirst on-off valve is opened to determine whether an attached catheteris still positioned in clot or otherwise occluded. The controller mayhold the first on-off valve open and the second on-off valve closed ifno occlusions or clogs are detected.

In specific embodiments, the vacuum aspiration systems of the presentinvention comprise a base unit which incorporates at least one on-offvalve and the controller. The base unit will typically be configured tobe mounted directly on or near a vacuum pump or console and will usuallyinclude a connecting cable in order to receive power from the vacuumconsole or line and optionally exchange information with the controllerand the vacuum console. The connecting tube typically has a proximal endconfigured to connect the vacuum source and distal end configured toconnect to the aspiration catheter. In such instances, the vacuumaspiration system will typically further comprise an external unitconfigured to be secured to the connecting tube at a location betweenthe distal end and the proximal end thereof. Exemplary external unitscomprise at least a portion of the sensing unit. For example, thesensing unit may comprise a first pressure sensor in the base unit and asecond pressure sensor in the external unit. In those instances, thecontroller will typically be configured to determine if a differentialpressure exists based on the signals from the first and the secondpressure sensor.

In a second aspect, the present invention provides a vacuum aspirationmethod. The vacuum aspiration method comprises engaging a distal end ofan aspiration catheter against an occlusion in the blood vessel. Avacuum is applied through an aspiration lumen of the aspiration catheterusing a vacuum source coupled to a proximal end of the aspiration lumenby a connecting tube. In this way, portions of clot and other occlusivematerial may be drawn into the aspiration lumen, through the connectingtube, and into a collection receptacle by the vacuum source. Flowthrough the connecting tube is sensed, and a valve is automaticallyclosed to stop flow through the connecting tube when the sensed flowexceeds a determined value while the vacuum source remains on. Flowthrough the connecting tube will be later reestablished by opening thevalve, and the steps are repeated until a desired amount of clot hasbeen aspirated.

In a third aspect, the present invention provides an assembly forgenerating pressure differentials that may result in pressure pulses toexecute an extraction cycle. The assembly may include a fluid injectionapparatus, a mechanical displacement apparatus, gravity induced pressurehead, or a combination thereof. A fluid injection apparatus may providea source of relative positive pressure for a catheter currently orpreviously under vacuum aspiration. For instance, the fluid may be at apressure above that of the vacuum aspiration system, between full vacuumpressure and ambient pressure, at ambient pressure, between ambientpressure and systolic pressure, at systolic pressure, or above systolicpressure. The fluid injection apparatus may utilize an aperture, avalve, a pump, a pressure chamber, or some such combination. Amechanical displacement apparatus may physically displace the volume ofa catheter system to provide relative increases and decreases ofpressure depending on the direction of displacement. In one example, amechanical displacement assembly assists vacuum recovery after acatheter has had its pressure increased above the pressure of the vacuumsource.

In some embodiments of the present invention, the controller includes analgorithm that is used to interpret pressure sensor signals to determinewhether the contents flowing through a catheter should be characterizedas unrestricted, restricted, or clogged. Generally, unrestricted flow isa high flow that may be characterized as excessive and may be primarilyor completely comprised of healthy blood, clot-free blood, or blood freeof vessel-obstructing clot that is not helpful to aspirate, restrictedflow may be comprised of a mix of healthy blood and clot or otherocclusive material, and a clog may be caused by a clot or otherocclusive material within an aspiration catheter, partially within anaspiration catheter, adjacent to an aspiration catheter, or in otherconnecting tubing attached to the aspiration catheter. In some examples,healthy blood is blood with a low enough proportion of cross-linkedfibrin such that it is not sufficiently integrated to cause ischemia orother similar vessel occlusions. When the algorithm detects unrestrictedflow, it may cause the system to initiate a sampling mode. When thealgorithm detects restricted flow, it may cause the system to enablefull vacuum aspiration. When the algorithm detects a clog, it may causethe system to generate a variety of pressure pulses with an extractioncycle. The algorithm may be responsive and adaptable to changingcircumstances, such as changing to a catheter of a different sizemid-procedure. The algorithm may adjust sampling modes and pressurepulse magnitudes if the catheter state remains static, changes tooquickly, changes to slowly, or improves as expected.

In specific aspects of the method, the present invention may remove clotand other occlusive material from a blood vessel that comprises a veinor an artery. Sensing of flow may comprise one or more of differentialpressure measurement, acoustic flow measurement, optical flowmeasurement, thermal flow measurement, measurement of circumferentialexpansion of the connecting tube, and the like.

In preferred aspects of the method, sensing flow comprises measuring thedifferential pressure using a first sensor located proximate the vacuumsource and a second sensor located on or adjacent the connecting tubebetween the vacuum source and the aspiration catheter.

In still further embodiments of the method, the resuming flow throughthe connecting tube comprises opening the valve for a sub-secondinterval, detecting when the sensed flow is characterized as acceptable,and automatically resuming flow. Automatically resuming flow typicallycomprises automatically detecting when the sensed flow can becharacterized as acceptable and the valve remains open as long as theflow is so characterized. Alternatively, resuming flow may comprisemanually opening the on-off valve.

In further embodiments of the method, pressure differentials aregenerated by closing a valve to a vacuum pump, opening a valve to asource of pressure, wherein the pressure is at least above that of thevacuum, and then re-opening the valve to the vacuum pump. Alternatively,or in combination, pressure differentials are generated by mechanicaldisplacement, wherein a volume of a chamber is reduced to increasepressure within a catheter and a volume of the chamber is increased todecreases pressure within a catheter, whereby the actuation of themechanical displacement chamber results in pressure differentials. Thepressure differentials may be tailored to have a specific or dynamicamplitude and frequency that facilitates the removal of clot or otherocclusive materials.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates the vacuum console and collection canister of thePenumbra System® mechanical thrombectomy system as described in detailin the Background of the Invention above.

FIG. 2 is a perspective view of a vacuum console and a blood and clotcollection canister with the collection canister received in a mountingregion of the vacuum console.

FIG. 3A is a view of the vacuum console of shown with the collectioncanister removed.

FIG. 3B is a detailed view of the on-off switch and a vacuum displayregion on a top surface of the vacuum console of FIG. 3 , shown with thepower off.

FIG. 3C is a schematic representation of the internal components of thevacuum console of FIGS. 1 to 3A.

FIG. 4 illustrates a collection canister.

FIG. 5 illustrates the embodiment of the collection canister of FIG. 4 ,shown in an inverted or “upside down” view.

FIG. 6 is an exploded view of the vacuum canister of FIGS. 4 and 5 .

FIGS. 7A and 7B illustrate a vacuum console and collection canister,similar to those illustrated previously, having a vacuum aspirationcontrol system attached thereto.

FIGS. 8A and 8B illustrate an external unit of the type suitable for usewith the present invention.

FIG. 9 illustrates an exemplary base unit enclosing an on-off valve anda controller of the type suitable for use in the vacuum aspirationcontrol system, shown in section.

FIG. 10 illustrates an exemplary external unit showing internalcomponents including a fitting and a pressure sensor, shown in phantom.

FIG. 11 illustrates an angle valve of the type which may be used ason-off valve in the present invention, shown in section.

FIG. 12 is an isometric view of an angle valve connected to a coiledtube having pressure sensors at each end thereof mounted on a canistertop.

FIG. 13 illustrates an example of an algorithm suitable for use with thepresent invention.

FIGS. 14-18 illustrate exemplary pulsed fluid injection assembliessuitable for use in the present invention.

FIG. 19 illustrates a mechanical displacement assembly for manipulatingpressure with the present invention.

FIG. 20 illustrates a graphical representation of one embodiment ofpulsed aspiration, where catheter internal pressure is varied over time.

DESCRIPTION OF EXAMPLE EMBODIMENTS

Some embodiments of the inventions of the present application aredescribed below. For clarity, not all features of each actualimplementation are described in this specification. In the developmentof an actual device, some modifications may be made that result in anembodiment that still falls within the scope of the invention.

Referring to FIGS. 2-6 , a vacuum system 40 of the type useful with theapparatus and methods for controlled clot aspiration of the presentinvention will be described. The vacuum system 40 includes a vacuumconsole 42 and a blood/clot collection canister 44. The vacuum console42 comprises an enclosure having a recess 48 which is shaped toremovably receive the collection canister 44 as will be described inmore detail below.

Referring to FIGS. 3A-3C, the vacuum console 42 is shown with the vacuumcanister 44 removed. A post 50 which forms a contiguous portion of theouter surface or wall of the enclosure 46 is formed within the recess 48and extends upwardly from a bottom plate 56 which acts as a support forthe collection canister 44 when it is received within the recess. Avacuum connector 52 and a pressure sensing connector 54 are formed in oron an upper surface of the post 50 and are located so that they willalign with a pressure sensing port 104 and a vacuum port 102 (FIG. 5 )on the vacuum canister 44 when it is received within the recess 48. Onelight 58 is located on a wall surface of the enclosure 44 within therecess 48 and is located so that it will illuminate the contents of thecollection canister 44 when the system is in use. A second light (notvisible in in FIG. 3A) is present on the opposite wall of the recess 48.The vacuum console 42 also has an on-off switch 60 on its upper surface.The on-off switch 60 illuminates when it is on (as shown in FIGS. 2 and3A) and is not illuminated when the system is off (FIG. 3B).Additionally, a pressure display 62 is provided on the upper surface ofthe enclosure 46. As shown in FIGS. 2 and 3A, the display may be acircular light, e.g. having four segments which are sequentiallyilluminated as the vacuum level within the canister increases. Eachquadrant represents the measured vacuum as a percentage of ambientpressure.

The internal components of the vacuum console 42 are schematicallyillustrated in FIG. 3C. The primary internal components of the vacuumconsole include a pressure sensor 64, a pump 68, a power supply 72, anda microprocessor controller 74. The pump 68 has an inlet connected tothe vacuum connector 52 on the post 50 of the enclosure 46. Similarly,the pressure sensor 64 is connected to the pressure sensing connector 54on the post 50. The pump can be turned on by the switch 60 and will drawvacuum through the connector 52 and release removed gas into an interiorof the console. The console in turn is vented by a vent 70 on a bottomsurface of the enclosure 46.

The functions of the pump will be controlled by the microprocessorcontroller 74, and the pressure output from sensor 64 will also gothrough the microprocessor controller 74. Each of the light 58, switch60, and display 62 will be connected to the microprocessor controller 74which is powered by the power supply 72. The power supply 72 is poweredthrough line current connector 72A. The USB connector 72B is powered bymicroprocessor controller 74. The pump is plugged into an outlet via apower cord that is supplied with the pump. The power supply converts theAC current from the wall outlet to DC current which is what themicroprocessor controller uses to power the pump, switch, lights, USBconnector, etc.

In specific examples, pressure sensor 64 is connected to themicroprocessor controller 74 and measures vacuum pressure in thecanister through the pressure sensing connector 54. A second pressuresensor (not shown) is also connected to the microprocessor controller 74and measures ambient pressure outside of the pump enclosure through aninternal tube that is routed to a vent in the base of the pump. Themicroprocessor controller takes the vacuum pressure reading from thepressure sensor 64 and divides it by the ambient pressure reading fromthe second pressure sensor to calculate the vacuum pressure in thecanister as a percent of ambient pressure.

Referring now to FIGS. 4-6 , the collection canister 44 has a main body78 which is typically formed from a polished, clear plastic materialwhich is molded into the illustrated shape. The main body 78 has an openupper end 76 which can be covered by a removable clear plastic lid 80.The clear plastic lid 80 is typically attached by a bayonet connector82, and a form or other gasket 84 will seal the lid to the open end ofthe main body 78.

A groove 94 is formed in one side of the main body 78 and is shaped sothat it can be placed over the post 50 in the recess 48 of the enclosure46 of the vacuum console 42. As best seen in FIG. 5 , the pressuresensing port 104 and the vacuum port 102 are located at the upper end ofthe groove 94 so that they align and connect with the vacuum connector52 and pressure sensing connector 54 on the post 50 when the canister 44is in place in the recess 48.

The pressure sensing port 104 is connected to a tube or lumen whichextends upwardly in the main body 48 of the canister 44 and terminatesin an upper opening or aperture 106. Similarly, the vacuum port 102extends upwardly through a much larger lumen or tube and terminates inan open aperture 108 at its upper end. The apertures 106 and 108 arelocated near the top of the interior of the main body 78 but will bebelow the bottom of the lid 80 when the lid is in place on the canister44. Thus, both of the apertures 106 and 108 will be exposed to theinterior of the canister 44 but will be maintained well above themid-section and bottom where the clot and blood are collecting. In thisway, the risk of contamination from blood and clot is minimized.

A filter plate 86, shown as a perforated screen but which could also bea woven screen or other separating member, is held in the mid-section ofthe interior of the main body 78 of the canister 44. The clot is drawninto the interior of the canister through a connector 110 which isattached to a proximal end of the catheter or other tubing. The clot andblood are drawn into the interior of the main body 78 by the vacuumwhich is drawn through the vacuum port 102 by the vacuum console 42, aspreviously described. As the clot and blood fall downwardly fromconnector 110 into the canister 44, the clot collects on the uppersurface of the filter plate 86 while the blood flows through theperforations in the plate and collects in the bottom of the canister. Asthe plate is inclined downwardly from a sleeve 88 which is mounted on apost 90 in the interior of the canister, excess blood may flow over anopen bypass region 100 (FIG. 4 ) which is formed on a backside of theplate and allows the blood to flow directly down to the bottom of thecanister. Filter body 92 occupies the interior of post 90 and aperture108 and prevents extracted material from contaminating the interior ofenclosure 42. Filter body 92 occupies the interior of post 90 andextends to aperture 108. The filter body can thus prevent extractedmaterial from contaminating the interior of enclosure 42. A groove 94 isformed on a side of the main body 78 of the canister 44 and is receivedover the post 50 in the recess 48 of the enclosure 46 in order to alignthe vacuum and pressure sensing connectors and vacuum ports. A gasket 96is further provided at the seal between the vacuum ports and the vacuumconnectors.

While the exemplary apparatus and methods for controlled clot aspirationdescribed in FIGS. 7-19 may be used with the vacuum system 40, as justdescribed, it will be appreciated that the inventions described andclaimed herein are not limited to use with any particular vacuum consoleand instead are useful with any clot or other vascular thrombectomy oraspiration system including a thrombectomy or other vascular aspirationcatheter in combination with a vacuum pump or other source where thereis a risk of excess blood aspiration, clogging, or both.

FIGS. 7A and 7B illustrate one example of an exemplary system 200 forperforming controlled clot aspiration in accordance with the principlesof the present invention comprises a base unit 210 and an external unit204. A proximal end of a connecting tube 206 is connected to the baseunit 210, and the external unit is secured on or to the connecting tubeat a location spaced apart from the proximal end, typically by somedistance sufficient to make conclusions about flow. The external unit204 may be configured to connect directly to a hub or other proximal endof an aspiration catheter or may be configured to be connected in themiddle of the connecting tube. The connecting tube is linear in anunconstrained configuration and flexible along its length.

The base unit 210 may be configured to sit directly atop the lid 26 onthe collection canister 44 of the previously described vacuum console40. Typically, a communication cable extends from the base unit 210through a portion of connecting tubing 206 to a connection receptacle onthe vacuum console 40 so that the base unit may be powered by the vacuumconsole and optionally can communicate data with the controller withinthe vacuum console.

As shown in FIG. 7B, an external unit 204 a may include a switch forinitiating treatment using the vacuum console 40 and controlled clotaspiration system 200. The switch may also turn off the system, therebyproviding a manual override of the algorithm that ensures the system isoff with no flow. When the switch is on, the system may immediatelyenter an algorithm mode where it decides to remain open, enter asampling mode, or initiate an extraction cycle in response to pressuresensor readings. Further details of the external unit 204 a are shown inFIGS. 8A and 8B.

Referring now to FIG. 9 , an exemplary base unit 200 b may comprise abase unit enclosure 216 having an open interior cavity 218 whichreceives a number of components. For example, a controller 220,typically including a microprocessor on a printed circuit board, may bemounted within the cavity 218 together with a pressure sensor 224secured between a tube segment 228 and a proximal end on the connectingtube 206 by a pressure fitting 226. The tube segment 232 may becollapsible and positioned in a pinch valve 228 which is driven by asolenoid 230. Pinch valve 228 may be biased into a closed position by acompressive spring (not visible), unless it is opened by solenoid 230.The base unit 200 b further includes a connecting fitting 222 which isconfigured to be removably secured to a vacuum fitting (not shown) onthe lid 26 of the canister 44. The controller 220 is configured to openand close the pinch valve 228 to allow and prevent, respectively, theflow of clot and blood through the tubing segment 232 from theaspiration catheter into the collection canister. Optionally, base unit200 b may include a button (not pictured) in electronic communicationwith printed circuit board 220, for advanced user control of variousparameters of the system. In further embodiments, a base unit of thepresent invention may house or be in communication with a pressurechamber, a fluid source, additional on-off valves, or some suchcombination.

Referring now to FIG. 10 , an exemplary external unit 204 includes anexternal unit enclosure 240 having a flow fitting 242 in an interiorcavity thereof. The flow fitting 242 may be connected to portions 206 aand 206 b of the connecting tubing 206, as shown for example in FIGS.7B, 8A and 8B. A second pressure sensor 246 may be mounted on a printedcircuit board 248 and also within an internal cavity of the enclosure240, and the output of the pressure sensor may be delivered to thecontroller 220 via a connective cable (not shown) which may be connectedvia a signal/power connector 250 and a mating signal-power connector252, which may be a conventional USB port and plug. The connecting cable206 may have dual lumens, as shown for example in FIG. 9 , where one ofthe lumens can be used to route a communications cable between theexternal unit and the base unit, while the other lumen accommodatesfluid flow. In further embodiments, an external unit of the presentinvention may house or be in communication with a pressure chamber, afluid source, additional on-off valves, or some such combination.

By providing a first pressure sensor 224 in the base unit and a second,axially separated pressure sensor 246 in the external unit 240, thematerial flow rate through the connecting tube can be calculated basedupon measured differential pressure by the controller. The controllermay analyze the pressure differentials and flow rate to determine thecontents flowing through the aspiration catheter, connective tubing, orboth.

In an exemplary embodiment, the controller characterizes the state of acatheter's contents as unrestricted flow, restricted flow, or clogged.In one example, a high-pressure differential between spaced-apartpressure sensors indicates unrestricted flow that may be comprised ofprimarily healthy, clot-free blood, or blood free of vessel-obstructingclot. In some examples, healthy blood is blood with a low enoughproportion of cross-linked fibrin such that it is not sufficientlyintegrated to cause ischemia or other similar vessel occlusions.Aspirating such healthy blood with full aspiration may result inexcessive blood loss that may require the premature termination of theaspiration procedure. In another example, a variable and intermediate orlow-pressure differential indicates restricted flow that may becomprised of clot, occlusive material, and blood. Such flow may benefitfrom full aspiration. In another example, a small pressure differentialor a pressure differential approaching zero indicates a clog. Such flow,or lack thereof, may benefit from an extraction cycle. The use ofdifferential pressure for detecting increased flow and occlusions,however, is exemplary and other flow measurement and material propertymeasurement techniques will be available within the scope of the presentinvention.

Referring now to FIG. 11 , instead of the pinch valve 228 shown in thebase unit 200, an angle valve 260 may be employed. The angle valve has aconnector 262 for being secured to a connector on the vacuum canister(not illustrated) as well as a fitting 266 that may be connected to theconnecting tubing 206 which is in turn connected to the aspirationcatheter. A solenoid 268 is typically present to open and close valvestem 270 and valve seat 272. In one example, the valves of the presentinvention open to permit aspiration and close to block aspiration.Alternatively, the valves of the present invention may open to allowfluid to enter the aspiration tubing and/or aspiration catheter andclose to block the fluid.

Referring now to FIG. 12 , the pressure sensors may be integrated into asingle base unit 276 which may be fixedly attached to a canister cap278. In this example, a first pressure sensor 282 and a second pressuresensor 284 are attached to opposite ends of a coiled flow tube 280 sothat differential pressure may be measured. An angled valve 286 may besecured directly to an outlet of the coiled flow tube 280 in order toprovide for the desired on/off flow control.

The controller 220 in base unit 200 may implement an algorithm thatreceives and analyzes pressure sensor data to open and close the on-offvalve, e.g. a pinch valve 228 (FIG. 9 ) or an angle valve 286 (FIG. 12 )or 260 (FIG. 11 ). The algorithm receives and analyzes the pressure datainput hundreds of times per second. The data are compiled to determinethe diameter of the attached catheter, determine the contents flowingthrough the catheter and aspiration tubing, and to determine the flowrate.

In one embodiment, the controller 220 implements an algorithm that usespressure sensor data to analyze the contents flowing through anaspiration catheter and characterizes it as unrestricted flow,restricted flow, or clogged. A catheter with unrestricted is aspiratingprimarily healthy, clot-free blood, or blood free of vessel-obstructingclot. A catheter with mixed flow is aspirating a combination of clot,occlusive material, and blood. A catheter with little to no flow isclogged or occluded. If the algorithm determines that an excessiveamount of blood is being aspirated, as is often the case for a catheterwith unrestricted flow, it may restrict aspiration to reduce blood loss.If the algorithm determines that a catheter has restricted flow, it willtypically allow full aspiration. If the algorithm determines that acatheter has little to no flow, it may initiate an extraction cycle tohelp remove any clogs or occlusions. As used herein, the term “clot”should be understood to encompass any occlusive material found invasculature, such as thrombus, embolus, plaque, occlusive material,vessel blockage, or any other obstructive material. Clot references allsuch occlusive material for brevity's sake.

FIG. 13 illustrates an example of an algorithm that uses pressuredifferentials (“AP”) to determine flowrate and, based on the determinedflowrate, controls the on-off valves of the present invention. In theillustrated algorithm logic tree, the first step is to measure max andminimum pressure differential windows over some assessment period and,after the assessment period, take an instantaneous pressure differentialand compare it to these max and minimum pressure differential windows,which are incrementally updated. If the instantaneous pressuredifferential is lower than the minimum pressure differential of theassessment period, the algorithm determines that the system is in clotand instructs the system to continue full aspiration. On the other hand,if the instantaneous pressure differential is above the minimum pressuredifferential the algorithm determines whether the instantaneous pressuredifferential is above the product of the max pressure differentialmultiplied by a confidence interval, if it isn't the algorithm allowsfull aspiration, if it is the algorithm restricts aspiration to limitblood loss and enters a sampling state where aspiration is limited tobrief surges to make new instantaneous pressure differential readings.In either case, whenever aspiration is allowed, the algorithmcontinually takes instantaneous pressure differential readings andcompares them to the max and minimum pressure differentials collectedthroughout the procedure. In one example, when unrestricted flow (e.g.open flow) is detected the algorithm triggers a sampling state. Inanother example, when a clot is detected the algorithm initiates fullaspiration or initiates an extraction cycle with pulsed aspiration.

In one embodiment, the present invention utilizes a correlationalgorithm that determines whether a catheter has unrestricted flow,restricted flow, or is clogged, e.g. the catheter's state, based on acorrelation between flow rate and such states. In another embodiment,the present invention utilizes a windowing algorithm that analyzesdiscreet portions of pressure sensor data to establish local minimum andlocal maximum pressure sensor readings. These windowed minimums andmaximums are compared to a global maximum and global minimum across thedata set. Given a sudden large delta in pressure readings, the systempreferentially makes determinations of a catheter's state according tolocal minimums and local maximums. Pressure readings below minimums andabove maximums signify a change in catheter state, e.g. below a minimumindicates a clogged catheter and above a maximum indicates anunrestricted flow state.

In an additional embodiment, the present invention utilizes an algorithmemphasizing an analysis of standard deviations across a discreet windowof data points. The flow rate is compared to the average and mean flowrate. A small standard deviation indicates a catheter that is clogged orunrestricted, while a large standard deviation indicates a catheter thathas restricted flow.

In one embodiment, a learning algorithm is used to determine thecontents flowing through an aspiration catheter. Training data is formedby collecting pressure readings along the length of catheter in avariety of states, e.g. unrestricted flow, restricted flow, or clogged.Numerous pressure readings are recorded for each catheter state, and thealgorithm then references those data sets to interpret never seenpressure readings to predict what state the catheter is in.

In another embodiment, the present invention utilizes an artificialneural network (ANN) that employs a multinomial logistic regressionalgorithm. The ANN is trained to predict answers by considering numeroustraining data sets. The training data includes both observed data asinputs and the actual outputs. The inputs are propagated across the ANN,which is comprised of layered nodes that each represent a lineartransformation within the solution space. The ANN then “learns” byanalyzing the difference between the ANN's calculated output and theactual output. This difference is translated into an error function. Theerror function is backpropagated across the ANN, whereby the weight ofeach node is modified according to its contribution to the errorfunction. Weighting is a process of mathematical optimization thatestablishes which nodes optimally map inputs to their correct outputs.Numerous sets of training data are propagated across the ANN iterativelyuntil the error function reaches convergence, i.e. some acceptable levelof tolerance. Once the nodes have been properly weighted, in that theerror function has reached convergence, the ANN can accurately predictthe output of previously unseen input. Here, that means that the learnedANN can take novel pressure sensor data inputs and accurately predictcatheter size and whether a catheter's contents should be classified asunrestricted, restricted, or clogged.

In some embodiments, the algorithm employs semi-supervised andunsupervised learning to continually update node weights. The algorithmmay employ clustering, dimensionality reduction, and reinforcementlearning to further improve prediction accuracy. In preferredembodiments, the algorithm can accurately interpret pressurefluctuations associated with switching between catheters of differentdiameters and filter out pressure fluctuations generated by manualmovements of a separator within the aspiration catheter by determiningand accounting for the cadence of the movement. Additionally, thepresent invention may employ an algorithm that uses a combination of theabove algorithmic flow analysis techniques.

The algorithm may initiate a sampling mode when unrestricted flow isdetected. In exemplary embodiments, the algorithm can detect a change inflow indicating unrestricted flow within milliseconds. In one embodimentof the sampling mode, the algorithm will cycle off aspiration and thenopen and close the on-off valve at a predetermined frequency. Thesampling state conducts an aspiration surge when the valve is brieflyopened and makes an assessment of the pressure sensor readings. Based onthis aspiration surge, the algorithm determines whether the systemshould revert to full aspiration, with the on-off valve in the openposition or remain in the sampling state. These sampling surges occurover a millisecond order of magnitude and ensure that full aspirationoccurs only when the system is engaging clot and thus minimizes bloodloss.

In an alternative embodiment, the system is powered on and has a briefdelay before the algorithm assesses flow in the aspiration tubing. Ifthe sensors indicate unrestricted flow, then an appropriate delay oftime is calculated for which the on-off valve remains shut. After thisdelay, the on-off valve opens to briefly allow aspiration and take apressure reading sample in the aspiration tubing to assess whether thesystem still has unrestricted flow or if it has been positioned intoclot or other occlusive material. If the sampling detects unrestrictedflow, a new delay is calculated (in some instances, incrementally longerfor each consecutive reading up to a threshold). If the sampling detectsclot, e.g. restricted flow or a clog, an appropriate delay of time iscalculated for which the valve remains open. While open, the systemassesses pressure sensors readings at a regular frequency to determinewhether the system has been positioned such to cause unrestricted flow.These processes repeat until the procedure is finished.

An extraction cycle may be useful to clear occlusions in an aspirationcatheter or to facilitate the aspiration of clot that are large orotherwise hard to aspirate. An extraction cycle establishes pressuredifferentials between the aspiration catheter and the vacuum source togenerate pressure pulses. In general, these pressure pulses can employmultiple mechanisms to facilitate thrombus ingestion into an aspirationcatheter. In one mechanism, the pressure pulse introduces anacceleration component that facilitates the extraction of occlusivematerial. In another mechanism, the pressure pulse creates a forceimpulse that breaks static friction momentarily, allowing a lowerdynamic friction to ingest thrombus. In yet another mechanism, thepressure pulse moves the thrombus away from the distal tip of thecatheter and subsequently rapidly forces contact between the thrombusand the catheter, macerating the thrombus.

In one example, an extraction cycle alternates between providing vacuumaspiration and relative positive pressure. An extraction cycle istypically initiated when an aspiration catheter is already under fullvacuum. When an extraction cycle is initiated, the vacuum on-off valvebetween the catheter and the aspiration source is closed and thepressure in the aspiration catheter is increased, which may cause apositive pressure pulse and establish a pressure differential betweenthe vacuum source and the catheter. When the on-off valve is thenopened, the contents and the distal tip of the aspiration catheterexperience the pressure differential as a negative pressure pulse thatnegatively impacts the structural integrity of any occlusions to adegree that a static force could only achieve with a greater supply ofenergy. The amplitude, or magnitude, of these pressure pulses aredirectly correlated to the pressure differential between an evacuatedcatheter and a pressure source (for positive pressure pulses) and apressurized catheter and a vacuum source (for negative pressure pulses).The frequency with which the on-off valve opens and closes may bepredetermined or responsive to pressure sensor data. An extractioncycle's pressure pulses may have an amplitude and frequency optimized toextract thrombus and similar occlusions from vasculature.

Pressure differentials in a catheter may be generated in a number ofways. In one example, pressure is generated by simply closing off acatheter's access to the vacuum source. In another example, pressure isgenerated by introducing fluid into the catheter, where the fluid is ata pressure between full vacuum and ambient pressure, at ambientpressure, at systolic pressure, or above systolic pressure (FIGS. 14-17). In another example, pressure differentials are generated bymechanical displacement of a pressure chamber (FIG. 18 ).

An extraction cycle may be automatically initiated when an algorithm ofthe controller 220 detects a clogged catheter, an occluded catheter, ora catheter positioned in clot. A catheter may be identified as inclogged state when the pressure differentials approach zero. In oneexample, the controller automatically initiates an extraction cycleafter the system has detected a clog lasting for more than 5 seconds.Alternatively, an extraction cycle is initiated, or terminated, ondemand by a user. An extraction cycle may provide pressure pulses for apredetermined time period. Alternatively, an extraction cycle assessespressure sensor data each time the on-off valve opens to assess flow andto determine whether the extraction cycle should continue or end. If anextraction cycle has trouble clearing a clog, it may vary the amplitudeand frequency of the pressure pulses. In one example, an algorithm onthe controller 220 consults a library of different pressure pulses andchooses from among the library. If a specific amplitude and frequencystarts to clear the clog, the algorithm may continue to generatepressure pulses of that frequency and amplitude until the clog iscleared.

FIG. 14 illustrates an example of a fluid system that may be used togenerate pressure differentials, and thus pressure pulses. In thisexample, a fluid introduction unit 290 is attached along a length of theconnection tubing 206 with a three-point junction 292. The three-pointjunction 292 may be positioned between the base unit 210 and theexternal unit 204 or may be positioned distal to both the base unit 210and the external unit 204—i.e. in close proximity to an attachedaspiration catheter. A fluid injection on-off valve 296 controls theflow of fluid (either liquid or gas) to inject pulses of pressure intothe clot flow path that may facilitate the extraction of clot or otherocclusive substances. In some instances, the flow of fluid is introduceddirectly into the connection tubing 206. In other instances, the flow offluid first traverses an injection tube 294 before entering theconnection tubing 206. The injection tubing 294 may direct the pressurepulse towards the catheter, which may optimize the pressure pulse. Inone example, the three-pint junction 292 has a T-joint structure asillustrated in FIG. 13 . Alternatively, a three-point junction may havea Y-joint structure (not illustrated). The Y-joint may beneficiallydirect fluid from the fluid introduction unit towards the catheter,which may optimize the pressure pulse in a similar manner to theinjection tubing of the prior example.

FIG. 15 illustrates an alternative fluid system that uses a pump 398that may be connected between a fluid reservoir 390 and an injectionvalve 396. In one embodiment, the pump 398 cycles on when the injectionvalve 396 opens. The pump provides work by forcefully injecting fluidfrom a fluid reservoir 390, through the injection on-off valve 396, intoan injection tube 394 and/or connection tubing 306. In this example, themagnitude of the positive pulse of pressure is directly correlated tothe throughput (e.g. size) of the pump 398. In a second embodiment, apressure chamber 397 is positioned between the pump 398 and theinjection valve 396. A pressure chamber 397 allows the pump 398 toprovide work even when the injection valve 396 is closed. While theinjection valve 396 is closed, the pump 398 forcefully injects fluidfrom the reservoir 390 into the pressure chamber 397, whereby thepressure chamber 397 becomes pressurized. When the injection valve 396opens, pressure is released from the pressure chamber 397 into theinjection tube 394 and/or connection tubing 306. In this embodiment,since the pump 396 can build up pressure over time, the magnitude of thepositive pulse of pressure is not directly correlated to the throughput(e.g. size) of the pump 398, thus this embodiment allows for a smallerpump. To provide even greater control over the duration or magnitude ofpositive pressure pulses, the opening and closing of the injection valvemay be throttled or manipulated to modulate rate of injection.Additionally, a pressure sensor may be included in pressure chamber 297to monitor and control the buildup of pressure.

FIG. 16 illustrates another three-point junction 492 attached alongconnection tubing 406. The three-point junction 492 may be positionedbetween the base unit 210 and external unit 204 or may be positioneddistal to both the base unit 210 and the external unit 204. A pressurevalve 496 controls the generation of positive pulses of pressure fromfluid chamber 490. Fluid from the fluid chamber 490 may flow directlyinto connection tubing 406 or may first traverse an injection tube 494before entering the connection tubing 406. An aspiration valve 499controls the application of vacuum aspiration from an attached vacuumsource. In this embodiment, the three-point junction 492 has valves tocontrol both vacuum forces and positive pressure pulses. This allows thethree-point junction 492 to alternate between applying vacuum aspirationand pulses of pressure, wherein the pressure is above that of the vacuumsource. The aspiration valve 499 and the pressure valve 496 may beopened alternatively, simultaneously, with a delay, or in someoverlapping sequence. In one overlapping sequence, one valve starts toopen when the other valve is starting to close, whereby there is a briefperiod where both valves are at least partially open. In otheroverlapping sequences, sometimes both valves are open and both valvesare closed for at least short periods of time.

In one embodiment, an aspiration valve 499 is positioned between acatheter and an aspiration source to modulate aspiration and a pressurevalve 496 is positioned between the catheter and fluid source tomodulate fluid injection. The present invention may selectively open andclose both aspiration valve 499 and pressure valve 496 to createpressure differentials within the catheter and/or aspiration tubing thatresult in pressure pulses of a desired amplitude and frequency.

FIG. 17 provides a perspective view of a three-way joint and thecomponents it connects. In this example, a connection tubing 706 acts asa common conduit between a vacuum source 700, a pressure source 790, andan aspiration catheter 750. The connection tubing 706 may have a firstend configured to attach, or be placed in fluid communication with, thevacuum source and a second end configured to attach, or be placed influid communication with, the aspiration catheter. In one example, thesecond end is attached to the aspiration catheter with a rotatinghemostasis valve. A three-way joint 792 may be positioned proximate tothe second end to provide pulses of relative positive pressure near theaspiration catheter 750. In one example, the three-way joint 792 is anangled joint or Y-joint, whereby fluid from the pressure source isdirected towards the aspiration catheter 750. In some examples, thethree-way joint 792 includes injection tubing 794, which directs fluidfrom the pressure source towards the aspiration catheter 750. In someexamples, the injection tubing 794 extends from the three-way joint intothe aspiration catheter, whereby fluid flows from the pressure sourceinto the aspiration catheter 750. In another example, the injectiontubing 794 extends from the three-way joint to a position proximate adistal end of the aspiration catheter, as depicted in perspective 751,which provides a zoomed-in perspective of the distal end of theaspiration catheter 750. In this example, the pressure source may causefluid to flow according to directional arrow 761 and the vacuum sourcemay cause fluid to flow according to directional arrow 760. In someembodiments, the controller may modulate a vacuum valve 799 and apressure valve 796, whereby the closing of the vacuum valve 799 and theopening of the pressure valve 796 may result in a relative increase inpressure at a distal tip of an aspiration catheter. Alternatively, theopening of the vacuum valve 799 and the closing of the pressure valve796 may result in a relative decrease in pressure at the distal tip ofthe aspiration catheter 750. In some instances, these changes inpressure are transmitted along a length of the aspiration catheter as apressure pulse. In some embodiments, a controller may close vacuum valve799 and open pressure valve 796 for a small period of time, thusallowing a minimal volume of fluid from the pressure source 790 to beintroduced into a proximal end of aspiration catheter 750 to increasethe relative pressure at a distal end of the aspiration catheter 750before reverting to vacuum by re-opening vacuum valve 799 and closingpressure valve 796. Similarly, a controller may close vacuum valve 799and open pressure valve 796 for a longer period of time, allowing alarger volume of fluid from the pressure source 790 to be introducedinto the aspiration catheter 750 to facilitate movement of obstructivematerial away from the distal end of aspiration catheter 751 beforereverting to vacuum by re-opening vacuum valve 799 and closing pressurevalve 796. In some embodiments, the connecting tubing 706 may have adual lumen along a portion of its length, whereby one lumen accommodatesfluid and a second lumen accommodates wiring, which enables thecontroller to modulate both the vacuum valve 799 and the pressure valve796.

FIG. 18 illustrates another embodiment of a valve structure thatcontrols both aspiration forces and positive pressure pulses. In thisexample, a three-point junction 592 attaches to connection tubing 506and pressure chamber 590. A gate valve 550 translates at axis 570 toblock aspiration in a 550A position and to block fluid introduction in a550B position. The gate valve 550 may provide pulsed aspiration byoscillating back and forth at a predetermined or responsive frequency ascontrolled by an algorithm in the controller 220. In this example, thethree-way gate valve exists at the juncture between the aspirationsource, the pressure source, and the catheter. The gate valve 550translates between blocking the aspiration source and blocking thepressure source to effect pressure pulses of a desired amplitude andfrequency.

In an alternative embodiment, fluid injection does not occur at athree-point juncture, but rather occurs at a more distal region closerthe catheter tip. The location of the relative pressure injection may beused to optimize the pressure pulse variation in order to facilitateclot removal. In one embodiment, a distal region of an aspirationcatheter includes a valve that can be opened and closed, e.g. the distalvalve. In one example, an aspiration valve is closed, and the distalvalve is opened to allow blood to rush into the catheter, whichincreases the pressure in the catheter and amplifies the pressuredifferential between the catheter lumen and the vacuum source.Typically, the distal valve is then closed, and the aspiration valve isopened, wherein the pressure differential between the vacuum source andthe catheter results in a pressure pulse. In another embodiment, fluidis transferred into an aspiration catheter from another adjacentcatheter. For instance, an inner catheter may deliver fluid to an outeraspiration catheter. Alternatively, an outer catheter may deliver fluidto an inner aspiration catheter through a valve structure. In eithercase, the fluid is delivered along the length of the aspirationcatheter, rather than through a proximal end. In a similar manner, anadjacent catheter may offer an additional connection to a vacuum source.

FIG. 19 illustrates a mechanical assembly for generating pressurepulses. In this example a mechanical piston 699 can replace the previousembodiment's injection valves, pressure chambers, pumps, and fluidreservoirs. The stroke of the piston 699 or alternative mechanicaldevice can be controlled to adjust the volume of the catheter resultingin the generation of negative pressure on one stroke and the generationof positive pressure on the other stroke. In general, a mechanicalactuation device actuates back and forth to increase and decrease theoverall volume of the system. When the device actuates to increasevolume, pressure decreases, and when the device actuates to decreasesvolume, pressure increase. These pressure changes may create, amplify,or assist pressure pulses of an extraction cycle. The piston 699 may beprovided in a three-point juncture 692 that attaches to connectiontubing 606. Other mechanical means of controlling volume, or pressure,of the catheter include linear motors, stepper/servo motors, camfollower actuators, solenoids, audio exciters, voice coil actuators,diaphragms, peristaltic pumps, rotary vanes, gears, screws, syringesetc. (not pictured).

High frequency pressure pulses may be enabled by a mechanical method,such as that depicted in FIG. 19 . To provide high frequency pressurepulses, a catheter must be rapidly pressurized and rapidly evacuated.The fluid injection systems of FIGS. 14-18 may readily provide a rapidinflux of pressure; however, it may take a non-insignificant amount oftime for the vacuum source to bring that catheter back to full vacuum.If the next influx of pressure occurs too early, the catheter will nothave had time reach full vacuum, or near full vacuum. In this scenario,the pressure differential between the not-quite-evacuated catheter andthe pressure source will be lower and the resulting pressure pulses willhave a lower amplitude, which may be suboptimal in some scenarios. Toavoid low amplitude pressure pulses caused by a high frequency, thepresent invention may utilize a vacuum recovery system to reduce thetime required to return a catheter to full vacuum after an influx ofpositive pressure. With a vacuum recovery system, the present inventionenables pressure pulses with both a high amplitude and a high frequency.

FIG. 19 illustrates a device that may function as a vacuum recoverysystem by generating pressure differentials. Alternatively, a vacuumrecovery system may utilize a syringe, an evacuated chamber, a secondaspiration pump, or some combination of these options. A syringe is apiston actuated device that retracts to increase a system's volume (andthus decrease pressure) and advances to decreases a system's volume (andthus increase pressure). A syringe-like device may beneficially assistnot only vacuum recovery but also positive pressure pulse generation. Inone example, a syringe is used during an extraction cycle. In such anexample, a catheter starts at full vacuum. The vacuum source closes, thesyringe advances (to reduce system volume), and, optionally, fluid isinjected, which all facilitates the formation of a positive pressurepulse. Next, the vacuum source opens, and the syringe retracts (toincrease system volume) to generate a negative pressure pulse, wherebythe syringe speeds the catheter's return to near full vacuum.Alternatively, an aspiration pump is configured to selectively prime anevacuated chamber that is opened to the catheter, in addition to anaspiration pump, after each pressure pulse. Together, the aspirationpump and the evacuated chamber more rapidly return a catheter to fullvacuum. While the aspiration pump is closed to the catheter, it may beopened to the evacuated chamber to further prime the evacuated chamberbetween pressure pulses. In a further alternative, a secondaryaspiration pump assists a primary aspiration pump to facilitate vacuumrecovery after each pressure pulse.

FIG. 20 illustrates a graphical representation of an example pulsationprotocol. An extraction cycle may use a pulsation protocol tosystemically manipulate the amount of pressure within a catheter tofacilitate the extraction of occlusive material. Pressure in a cathetermay be manipulated by a variety of methods. For instance, vacuumaspiration may be used to reduce pressure within the catheter and theremoval of vacuum suction and/or the introduction of fluid may be usedto increase pressure within the catheter. In other instances, amechanically actuating device may alternate between increasing anddecreasing pressure within a catheter. In the example illustrated byFIG. 20 , at time 0, the catheter has not been subjected to any suctionforces and is at atmospheric pressure. From time 0 to time 1, thecatheter has lost pressure, lunging from atmospheric pressure to nearfull vacuum (i.e. near −29.9 inHg). From time 1 to time 2, the catheterhas gained pressure, which decreases vacuum strength. From time 2 to 3,the catheter has lost pressure, which returned the catheter to near fullvacuum. From time 3 to 4, the catheter has gained pressure and returnedto ambient pressure. From time 4 to 5, the catheter has lost pressure,again lunging from atmospheric pressure to near full vacuum. From time 5to 6, the catheter has gained pressure, which caused the pressure tosurge from near full vacuum to above ambient pressure. From time 6 to 7,the catheter has lost pressure, lunging from a pressurized state aboveatmospheric pressure to near full vacuum.

A pulsation protocol of the nature illustrated in FIG. 20 may beexecuted once or may be repeated several times. In alternativeembodiments, the pulsation protocol may include additional time periodswith additional pressure variations and pressure patterns. In general,the system's pressure may vary from between near vacuum to above averagesystolic pressure. The duration of the pulsation protocol may bepredetermined or adaptive to pressure sensor readings. For instance, thecontroller may prolong or shorten a pulsation protocol based on pressuresensor readings. In some examples, the system may remain at a stablepressure state across one or more time periods. For instance, thecontroller may cause the system to dwell at near full vacuum. The dwelltime in each pressure state and the frequency with which the systemtransitions between pressure states may be optimized to ingest differentclot or occlusive material compositions. Although FIG. 20 illustrates apulsation protocol with a stable and consistent frequency, in otherexamples the frequency of a pulsation protocol is variable or somecombination of partially stable and partially variable. High amplitude(or high magnitude) pressure pulses may be generated by generating largepressure differentials. For instance, FIG. 20 illustrates a highamplitude pressure pulse between times 5 and 7. Lower magnitude pressurepulses may be generated by oscillating between less extreme highpressures and low pressures. For instance, the low end of the pressurepulse may not reach near full vacuum, the high end of the pressure pulsemay not reach ambient pressure, or both, thereby resulting in a lowermagnitude pressure pulse, which may be desirable in some scenarios. Thetime units of FIG. 20 may be in second, milliseconds, microseconds, orthe like.

In some examples, an extraction cycle uses a predetermined series ofpressure pulses with near full vacuum aspiration before the extractioncycle, between individual pulses of relative positive pressure, andafter the extraction cycle. The pressure pulses may be selected from alibrary of pressure pulses having amplitudes and frequencies thatfacilitate the extraction of clot and other occlusive material. A seriesof pressure pulses may vary from one another in terms of frequency,amplitude, or both. For instance, a pulsation protocol may use a seriesof pressure pulses with a trend where one of the amplitude or frequencyrises while the other diminishes, where both the amplitude and frequencyrise or diminish, or where one of the amplitude or frequency rises ordiminishes while the other remains constant.

In some examples, an extraction cycle provides specific pressure pulsesbased on pressure sensor readings. One such responsive extraction cyclemeasures pressure within the catheter and then selects one or morepressure pulses optimized for a catheter with those pressure readings.In another responsive extraction cycle, the system cycles through alibrary of pressure pulse protocols, with time periods of static or fullaspiration and occlusion detection after each individual pressure pulse.After the library has been cycled, the system repeats the pressurepulses that were measured to be most successful. The degree of successof a specific pressure pulse is typically commensurate with the amountof increased flow rate after the pressure pulse. The system willcontinue to cycle down until only a few pressure pulse protocols are inthe loop. If the efficacy of the loop begins to diminish, the systemwill return to the full library and start a fresh cycle.

In an alternative responsive system, a responsive extraction cycle hasthree modes: Cycling up, where successive pressure pulses are strongerin terms of amplitude and/or frequency, cycling down, where successivepressure pulses are weaker in terms of amplitude and/or frequency, andmaintenance pressure pulses, where pressure pulses have a consistentfrequency and amplitude. When the system detects a clogged state, itenters the cycling up mode. When the system detects restricted flowstate, it enters the maintenance mode. When the system detects anunrestricted flow state, it enters the cycling down mode. In this way,the system trends towards pressure pulses with an amplitude andfrequency that facilitates restricted flow, which is beneficiallyremoving clot and other occlusive material.

In situations where maximizing the removal of occlusive materialeclipses concerns of blood loss, such as in neurovascular strokeprocedures, an alternative embodiment according to the invention may beuseful. Under these circumstances, as an example, an optimal techniquemay include positioning the distal end of a catheter in clot, applyingfull vacuum, and waiting a predetermined period of time before advancingto a next step. The objective may be complete or nearly completecatheter tip engagement of a mass of occlusive material, engagementwhich essentially clogs the distal end of the catheter and is sometimesreferred to as “corking the catheter”. If a clinician has successfully“corked the catheter”, the catheter system may be removed from thevessel, withdrawing the mass of clot or occlusion with it.Alternatively, an extraction cycle may be used to draw an occlusionthrough the catheter lumen or cause the clot to become deeply latched,or corked, within the catheter attached to the present invention. Afterthe completion of the extraction cycle, the clot should be removed orcorked in the attached catheter so that the catheter together with theclot can safely be removed from the patient.

In some instances, an extraction cycle may automatically stop or bemanually stopped when a clot or other occlusive material clogs acatheter and corks it. For instance, the clot or occlusive substancemight be too large or tough to traverse an aspiration catheter, butnonetheless become partially entrained in the aspiration catheter. Insuch instance, the system may transition to full aspiration to allow theuser to remove the corked catheter while dragging the clot or occlusivematerial out with the catheter. In one example, an extraction cycle isinitiated, and the clot or occlusive material still clogs the catheter.The controller may then revert to full aspiration and notify the user ofthe corking event, whereby the system may prompt the user to remove thecatheter. Alternatively, the user may manually turn off an extractioncycle, causing the system to return to full vacuum, and remove thecatheter.

To indicate that the present invention is doing work to remove clots orother occlusive material, one embodiment includes visual and/or auditorysignals that indicate the progress of a given extraction cycle. In oneexample, the start of an extraction cycle is signaled by a flashing bluelight, which flashes until the cycle is completed, and, at completion,the light turns to green to indicate completion. In another example,base unit 216 may include a light bar. The light bar fills upincrementally, whereby the light bar progressively “fills up” with lightin proportion to the cycle's progress. Alternatively, base unit 216 mayinclude a small screen for displaying images. The small screen maydisplay an animation indicative of loading. Loading animations mayexecute a repetitive pattern (e.g. spinning circular object) or mayexecute a single cycle of a prolonged animation (e.g. slowly fillingcircle). Either in conjunction with visual progress indication or as analternative to visual progress indication, the system may use auditorycues to signify the extraction cycle's initiation, pulsating phase, andcompletion. Such auditory cues may include musical notes, beeps, and/orspeech. Auditory cues may include updates (e.g. “extracting”) orsuggestions (e.g. “advance/retract the catheter”).

An algorithm may also control a lighting mechanism, e.g. indicator light210 (FIGS. 7A and 7B), to convey to the user whether the system is in afull aspiration state, an unrestricted flow state, a restricted flowstate, a clogged state, a sampling state, or an extracting state.Specific lights may be illuminated to indicate bubbles or that theoverride switch has been triggered. Additionally, the algorithm maycontrol a piezo acoustic chip that conveys audible information to thephysician regarding the state of the effluent and override switch. Inone embodiment, the piezo is a surface mounted 4 kHz single tone at 65dB at 10 cm. The signals may include sounds and phrases such astone/pitch changes, beeping patterns, “clogged”, “occluded”, “clot”,“blood”, “open flow”, etc. One example utilizes a dynamic beepingcadence, where a beeping pattern is steadily increased when anunrestricted flow state is increasing in duration. The speed of thebeeps indicates the length of time the system has been in unrestrictedflow, alerting the physician to the increasingly problematic nature ofthe system's positioning. The system may also include a multi-positionswitch or button to specifically activate different algorithms, muteaudio cues, or to prime the system with fluid. Such a feature could beactivated by inserting a pin in the base unit 210, which will activatethis customizable feature.

In one embodiment, the system may be manually powered on and conductaspiration for a predetermined period of time. If the system detectsunrestricted flow, then the on-off valve is turned off to stop flow. Theattending physician then must reposition the catheter tip into clot andmanually trigger a mechanism (such as a foot pedal or manual switch) toinitiate further aspiration. This manual trigger overrides the algorithmand allows aspiration to continue. Once the manual trigger is released,the algorithm again monitors flow to allow aspiration so long as theflow is acceptable. If and when the system again detects unrestrictedflow, the on-off valve is again closed until the physician repositionsthe aspiration catheter and manually overrides the controller. Thisprotocol is repeated until the physician completes the procedure.

Before an aspiration catheter can be used to remove clot and otherocclusive material it must be primed with an uncompressible fluid. Forinstance, a catheter may be filled with saline fluid to remove all theair from the lumen of the catheter. In some embodiments, the presentinvention automatically primes a catheter, whereby the catheter isfilled with fluid to expel all compressible fluids, like air. In oneexample, the sensors of the present invention monitor catheter contentsduring use. If compressible fluids are detected, like bubbles, thesystem may alert the user. In some instances, the system may indicatethat the procedure needs to stop so that the catheter can be againprimed to remove the air bubbles.

The foregoing examples are not intended to limit the scope of theinvention. All modifications, equivalents and alternatives are withinthe scope of the invention.

What is claimed is:
 1. An aspiration thrombectomy system, comprising: anaspiration catheter having a proximal portion, a distal end and a lumenextending through the catheter; a vacuum source fluidically coupled tothe catheter; a vacuum valve connected between the vacuum source and theproximal portion of the catheter to control a vacuum flow in thecatheter lumen; a vent valve fluidically coupled to the proximal portionof the catheter, the vent valve being configured to control a flow of avent fluid in the catheter lumen; and a controller configured to openand close the vacuum valve and the vent valve in a predetermined cycleto change a level of vacuum at the distal end of the catheter and tocontrol fluid flow in and out from the distal end of the catheter. 2.The system of claim 1, further comprising a vent fluid source, andwherein: the vent fluid source is configured to provide vent fluid at apressure greater than atmospheric pressure; and the controller isconfigured to cyclically open and close the vacuum valve and the ventvalve to change a level of negative pressure and positive pressure atthe distal end of the catheter during each cycle.
 3. The system of claim2 wherein the controller is configured to cyclically open and close thevacuum valve and the vent valve such that movement of the fluid columnat the distal end of the catheter is limited to a positive amount ofexit flow before fluid is drawn back into the catheter lumen.
 4. Thesystem of claim 1 wherein the controller is configured to cyclicallyopen and close the vacuum valve and the vent valve in a repeated cyclecomprising an off-off state in which the vacuum valve is closed whilethe vent valve is closed.
 5. The system of claim 1 wherein: thecontroller is configured to cyclically open and close the vacuum valveand the vent valve in a cycle comprising (a) a first off-off state inwhich the vacuum valve is closed while the vent valve is closed, (b) avacuum-only state following the first off-off state in which the vacuumvalve is open while the vent valve is closed, (c) a second off-off statefollowing the vacuum-only state in which the vacuum valve is closedwhile the vent valve is closed, and (d) a vent-only state following thesecond off-off state in which the vacuum valve is closed while the ventvalve is open; and the cycle is repeated.
 6. The system of claim 5wherein the cycle is repeated at a predetermined frequency.
 7. Thesystem of claim 1 wherein the vacuum valve and the vent valve aresolenoid pinch valves.
 8. The system of claim 1 wherein the vacuum valveand the vent valve are cammed pinch valves.
 9. The system of claim 1wherein the controller is configured to cyclically open and close thevacuum valve and the vent valve such that an amount of accelerationforce is sufficient to aspirate thromboembolic material at the distalend of the catheter.
 10. A method for removing thromboembolic material,comprising: aspirating thromboembolic material from a person using thesystem of claim 1 by— (a) positioning the distal end of the catheter atleast proximate to thromboembolic material in a blood vessel of theperson; (b) applying a vacuum through the lumen of the catheter suchthat a vacuum flow draws at least a portion of the thromboembolicmaterial into the catheter lumen; and (c) controlling the vacuum valvefluidically coupled to the vacuum source and the catheter and the ventvalve fluidically coupled to a vent fluid source and the catheter suchthat a level of vacuum at the distal end of the catheter changes andthereby controls flow in and out from the distal end of the catheter.11. The method of claim 10 wherein: the vent fluid source is configuredto provide the vent fluid at a pressure greater than atmosphericpressure; and controlling the vacuum valve and the vent valve comprisescyclically opening and closing the vacuum valve and the vent valve tochange a level of negative pressure and positive pressure at the distalend of the catheter during each cycle.
 12. The method of claim 11wherein controlling the vacuum valve and the vent valve compriseslimiting movement of a fluid column in the catheter lumen at the distalend of the catheter to a positive amount of exit flow that exits thedistal end of the catheter.
 13. The method of claim 12 wherein themovement of the fluid column at the distal end of the catheter islimited before fluid is drawn back into the catheter lumen.
 14. Themethod of claim 10, further comprising cyclically opening and closingthe vacuum valve and the vent valve in a repeated cycle including anoff-off state in which the vacuum valve is closed while the vent valveis closed.
 15. The method of claim 10, further comprising: cyclicallyopening and closing the vacuum valve and the vent valve in a cycleincluding (a) a first off-off state in which the vacuum valve is closedwhile the vent valve is closed, (b) a vacuum-only state following thefirst off-off state in which the vacuum valve is open while the ventvalve is closed, (c) a second off-off state following the vacuum-onlystate in which the vacuum valve is closed while the vent valve isclosed, and (d) a vent-only state following the second off-off state inwhich the vacuum valve is closed while the vent valve is open; andrepeating the cycle.
 16. The method of claim 15 wherein the cycle isrepeated at a predetermined frequency.